(i) Field of the Invention
The present invention relates to a method for preparing .alpha.-(4-isobutylphenyl)propionic acid or its precursor, i.e., an alkyl .alpha.-(4-isobutylphenyl)propionate or .alpha.-(4-isobutylphenyl)propionaldehyde at a low cost and in a high purity.
.alpha.-(4-Isobutylphenyl)propiopic acid is a useful medicine (trade name Ibuprophen) having pharmacological effects such as alleviation effects of fever and pain and antiphlogistic effect, as described in British Patent No. 971700 and French Patent No. 1549758.
On the other hand, it is known that the alkyl .alpha.-(4-isobutylphenyl)propionate can be easily converted into .alpha.-(4-isobutylphenyl)propionic acid by hydrolysis with an acid or an alkali in a known manner. Furthermore, it is also known that .alpha.-(4-isobutylphenyl)propionaldehyde can be easily converted into .alpha.-(4-isobutylphenyl)propionic acid by oxidization in a known manner. Therefore, each of these compounds can be considered to be the precursor of .alpha.-(4-isobutylphenyl)propionic acid.
(ii) Description of the Prior Art
Heretofore, .alpha.-(4-isobutylphenyl)propionic acid or its precursor has been synthesized from an extremely great number of compounds as starting materials by various methods. However, in order to synthesize .alpha.-(4-isobutylphenyl)propionic acid or its precursor at a low cost and in a high purity, the following requirements are needful:
(a) Starting materials should be simple compounds.
(b) In a reaction to be utilized, an intermediate in the each step should also be as simple and stable as possible.
(c) In place of expensive reagents, inexpensive reagents or catalysts should be employed.
(d) The number of steps for the synthesis should be as few as possible.
(e) Since an isobutyl group is liable to bring about isomerization, it is necessary to use a reaction in which the isomerization and other undesirable phenomenons are inhibited to the utmost.
For example, in U.S. Pat. No. 3959364 which suggests synthetic methods of .alpha.-(4-isobutylphenyl)propionic acid or its alkyl ester, expensive starting materials are used, or reagents such as Grignard reagents which are unstable and difficult to handle are used. Therefore, these methods are not considered to be inexpensive and economical.
In methods described in French Patent No. 1549758, British Patent Nos. 1160725 and 1549140 and U.S. Pat. Nos. 3965161 and 4143229, p-isobutylacetophenone is used as the starting material.
However, in the manufacture of p-isobutylacetophenone, expensive and unstable material and reagent are used, and it is additionally necessary to treat a large amount of acidic wastes so as to make them harmless. Furthermore, the conversion of p-isobutylacetophenone into .alpha.-(4-isobutylphenyl)propionic acid proceeds via intricate intermediates, and it is not always fair to say that these known methods are economical from an industrial viewpoint.
U.S. Pat. No. 4329507 suggests a method for preparing .alpha.-(4-isobutylphenyl)propionic acid from p-isobutylstyrene through a carbonylation reaction. This method is industrially useful, because p-isobutylstyrene which is the starting material is simple and stable, and because the carbonylation reaction does not require expensive reagents. However, in a conventional manufacturing method of p-isobutylstyrene, a complex reaction route is taken or expensive reagents are employed, so that the above-mentioned advantages are lost.
U.S. Pat. No. 4694100 discloses a method which comprises subjecting isobutylbenzene and acetaldehyde to condensation reaction in the presence of a sulfuric acid catalyst to form 1,1-bis(p-isobutylphenyl)ethane, and then catalytically decomposing the latter by the use of an acid catalyst to prepare p-isobutylstyrene. However, since the above-mentioned method employs sulfuric acid, the sulfonation reaction of isobutylbenzene itself which is the valuable raw material cannot be avoided in the step of forming 1,1-bis(p-isobutylphenyl)ethane, which leads to a heavy loss. In addition, since this condensation reaction is a dehydration reaction, the used sulfuric acid is diluted with the resulting water, so that its concentration is low. Additionally, a great deal of the sulfonated compound is dissolved in the sulfonic acid phase, and therefore the resulting water must be removed through chemical reaction by the use of anhydrous sulfuric acid or fuming sulfuric acid, with the result that the cost of the catalyst also increases.
In consequence, it is desired to develop a method for preparing p-isobutylstyrene at a low cost.
The present inventors have conceived the dehydrogenation of p-isobutylethylbenzene as a direct method for manufacturing p-isobutylstyrene inexpensively. However, the prior art regarding the dehydrogenation of p-isobutylethylbenzene is not present at all, and any similar techniques are not known, either. In other words, there are not known techniques so far which selectively dehydrogenate one specific substituent of a polyalkylbenzene such as p-isobutylethylbenzene having a plurality of alkyl groups which are different in structure and which may be all dehydrogenated.
For example, European Patent No. 93518 discloses a method for preparing methylstyrene by dehydrogenating methylethylbenzene; British Patent No. 2068253 discloses a method for preparing tert-butylstyrene by dehydrogenating tert-butylethylbenzene; and European Patent No. 217492 discloses a method for preparing ethylstyrene or divinylbenzene by dehydrogenating diethylbenzene. However, each of methylethylbenzene and tert-butylethylbenzene has an ethyl group which may be dehydrogenated and other substituents of a methyl group and a tert-butyl group which cannot be dehydrogenated. Therefore, the selectivity of the dehydrogenation reaction itself is not considered. Furthermore, with regard to diethylbenzene having two ethyl groups which may be dehydrogenated, it is unnecessary to consider the selectivity, because the two ethyl groups are not different.
However, the technique of the present invention for preparing p-isobutylstyrene by the selective dehydrogenation of p-isobutylethylbenzene is basically different from these known techniques. In the concrete, the substituents bonded to the aromatic ring of p-isobutylethylbenzene which is the raw material are an ethyl group and an isobutyl group, and these groups can be converted into a vinyl group and a 2-methyl-1-propenyl group or a 2-methyl-2-propenyl group (hereinafter referred to as "substituted propenyl group" sometimes) by the dehydrogenation. That is, when the ethyl group alone of p-isobutylethylbenzene is dehydrogenated, p-isobutylstyrene is formed, and when the isobutyl group alone is dehydrogenated, 4-(2'-methyl-1'-propenyl)ethylbenzene or 4-(2'-methyl-2'-propenyl)ethylbenzene is formed. Furthermore, when both of the ethyl group and the isobutyl group are dehydrogenated, 4-(2'-methyl-1'-propenyl)vinylbenzene or 4-(2'-methyl-2'-propenyl)vinylbenzene is formed. As is apparent from the foregoing, p-isobutylethylbenzene has the two different alkyl groups which can be dehydrogenated, and the product utterly depends upon the group to be dehydrogenated.
As understood from known literature such as Journal of Catalysis 34, p. 167-174 (1974) and Azerb. Khim. Zh., (2), p. 59-62 (Russ) (1968), a branched isopropyl group is dehydrogenated about twice to thrice more easily than a straight-chain ethyl group. According to the investigation of the present inventors, it has been confirmed that when p-sec-butylbenzene is dehydrogenated in the presence of an iron oxide catalyst, the sec-butyl group is about twice more easily dehydrogenated than the ethyl group. From this fact, it can be presumed that the branched sec-butyl group having 4 carbon atoms is more easily dehydrogenated than the straight-chain ethyl group, as described in the above-mentioned literature regarding isopropylethylbenzene. However, such a conception cannot achieve the object of the present invention.
That is, the product which is intended by the dehydrogenation step of p-isobutylethylbenzene is p-isobutylstyrene in which the ethyl group alone is dehydrogenated. Therefore, it is strongly demanded to develop a dehydrogenation method of p-isobutylethylbenzene in which the selectivity of p-isobutylstyrene is high, i.e., a method for selectively dehydrogenating the ethyl group alone of the ethyl and isobutyl groups.
Furthermore, another manufacturing method of p-isobutylethylbenzene is known which comprises reducing 1-(4-ethylphenyl)-2-methylpropane-1-one with potassium hydroxide and hydrazine in a solvent of diethylene glycol, as described in, for example, Beilstein, EIV5 (Sys. Nr. 470/H445). However, in this method, 1-(4-ethylphenyl)-2-methylpropane-1-one which is the raw material is very expensive, and hydrazine which is very dangerous to handle must be used as a reducing agent, which disturbs the industrialization of this method unpreferably. Moreover, it is known that p-isobutylethylbenzene is obtained as a by-product in the catalytic cracking reaction of 1,1-bis(p-isobutylphenyl)ethane, as disclosed in examples of U.S. Pat. No. 4827065. However, in this method, p-isobutylethylbenzene is the by-product, and therefore the production is unpreferably too low. As understood from the foregoing, the manufacturing examples of p-isobutylethylbenzene by the conventional techniques are very limited and are uneconomical. Therefore, it is strongly demanded to develop a method for manufacturing p-isobutylethylbenzene inexpensively.